Transcriptional analysis of four family 4 P450s in a Puerto Rico strain of Aedes aegypti (Diptera: Culicidae) compared with an Orlando strain and their possible functional roles in permethrin resistance.

A field strain of Aedes aegypti (L.) was collected from Puerto Rico in October 2008. Based on LD50 values by topical application, the Puerto Rico strain was 73-fold resistant to permethrin compared with a susceptible Orlando strain. In the presence of piperonyl butoxide, the resistance of Puerto Rico strain of Ae. aegypti was reduced to 15-fold, suggesting that cytochrome P450-mediated detoxification is involved in the resistance of the Puerto Rico strain to permethrin. To determine the cytochrome P450s that might play a role in the resistance to permethrin, the transcriptional levels of 164 cytochrome P450 genes in the Puerto Rico strain were compared with that in the Orlando strain. Of the 164 cytochrome P450s, 33 were significantly (P < 0.05) up-regulated, including cytochrome P450s in families four, six, and nine. Multiple studies have investigated the functionality of family six and nine cytochrome P450s, therefore, we focused on the up-regulated family 4 cytochrome P450s. To determine whether up-regulation of the four cytochrome P450s had any functional role in permethrin resistance, transgenic Drosophila melanogaster Meigen lines overexpressing the four family 4 P450 genes were generated, and their ability to survive exposure to permethrin was evaluated. When exposed to 5 microg per vial permethrin, transgenic D. melanogaster expressing CYP4D24, CYP4H29, CYP4J15v1, and CYP4H33 had a survival rate of 60.0 +/- 6.7, 29.0 +/- 4.4, 64.4 +/- 9.7, and 11.0 +/- 4.4%, respectively. However, none of the control flies survived the permethrin exposure at the same concentration. Similarly, none of the transgenic D. melanogaster expressing CYP4J15v1 or CYP4H33 ?5 survived when they were exposed to permethrin at 10 microg per vial. However, transgenic D. melanogaster expressing CYP4D24 and CYP4H29 had a survival rate of 37.8 +/- 4.4 and 2.2 +/- 2.2%, respectively. Taken together, our results suggest that CYP4D24 might play an important role in cytochrome P450-mediated resistance to permethrin.

Firearm laws, patients, and the roles of psychiatrists.

OBJECTIVE: Persons with mental illness and/or substance abuse are frequently perceived by the public to be dangerous. This has resulted in an increase in state legislation restricting their ability to purchase, possess, register, obtain licensure, retain, and/or carry a firearm of any sort. The purpose of this article is to educate clinicians about the impact of firearms statutes and restrictions for their patients. Many state statutes mandate that treating psychiatrists report such gun possession to state justice or police departments. Psychiatrists may also have a statutory role in an appeals process. METHOD: The firearms statutes of the 50 states, the District of Columbia, and Puerto Rico and the Federal National Firearms Act were surveyed, with particular attention paid to the ability of persons with mental illness and/or alcohol or substance abuse to obtain firearms. The results were tabulated. RESULTS: These statutes are not uniform. They vary in their definition of mental illness, the type and duration of gun restriction, reporting practices, the confidentiality of medical information, and the immunity of clinician reporters and appeals processes. CONCLUSION: Clinicians would be wise to familiarize themselves with the provisions of the relevant statutes in their particular states. This will allow them to identify the consequences to their firearm-possessing patients, understand their own roles and obligations -- if any -- and better consider potential clinical and ethical issues for particular patients.

Socioeconomic correlates of fertility, mortality, and child survival in mothers from a disadvantaged, urban Guatemalan community.

Social and economic determinants of fertility, mortality, and child survival were studied in a sample of 519 mothers from EL Progreso, a disadvantaged community located on the outskirts of Guatemala city. Fertility (children ever-born) and mortality (number of children who had died postnatally) data were obtained from interviews, along with data on the characteristics of the mothers, fathers, and the households. Contraceptive use was recorded on a subsample of 167 mothers of 5-year old children. Following factor analyses, three variables were selected for analysis: Years of schooling of the father and the mother and the type of fuel used for cooking. Father's education and type of fuel were significantly related to maternal fertility, while only the educational attainment of the mother was related to child mortality and survival. When contraceptive use was included in the ANCOVA in the subsample, it was a significant determinant of fertility, while father's education became nonsignificant. In terms of mortality, contraceptive use was a significant determinant, while the significance of the mother's education fell to a borderline value (P = 0.084).